This is an application for a K23 mentored patient-oriented research career development award for Dr. Yvonne Huang, M.D., a pulmonary/critical care medicine physician at the University of California, San Francisco. Dr. Huang is establishing herself as a clinical investigator of the role of airway microbial colonization (airway microbiota) in asthma. This K23 award will provide Dr. Huang with the support necessary to accomplish the following career development goals: (1) to obtain training and practical experience in leading clinical- translational research studies of asthma; (2) to learn and apply advanced statistical methods to analyze clinical data in conjunction with airway microbiome data generated from microarray and next-generation sequencing approaches; and (3) to acquire further knowledge and experience on methods for studying global functional gene expression in the airway environment. To achieve these goals, Dr. Huang has assembled a multidisciplinary mentoring team with complementary expertise in each of these three areas. This team is comprised of a primary mentor, Dr. Homer Boushey, Professor of Pulmonary Medicine at UCSF and an internationally recognized clinical investigator of asthma, and two co-mentors: Dr. Mark Segal, Professor of Biostatistics at UCSF and Director of the Center for Bioinformatics and Molecular Biostatistics, an expert in advanced statistical techniques for the analysis of complex molecular and genomic data; and Dr. Susan Lynch, Assistant Professor of Medicine at UCSF, an expert microbiologist who directs the microbiome research core in the Division of Gastroenterology, Department of Medicine at UCSF. Asthma is a common airway disease of still unknown etiology that bears significant socioeconomic burden. Clinical heterogeneity in asthma is now well-recognized, leading researchers to consider that different pathogenetic mechanisms may exist. One area of increasing interest is the potential role of airway bacterial colonization in the pathogenesis of asthma or of specific asthma phenotypes. Dr. Huang's research will examine if the composition of bacterial microbiota found in respiratory specimens from asthma patients are influenced by the use of inhaled corticosteroids or macrolide antibiotics, two medications used in the management of asthma (Aims 1 and 2). She additionally will study global functional gene expression profiles in the asthma airway microbiome to examine how they may relate to clinical features of disease (Aim 3). Dr. Huang will use the infrastructure of the UCSF Airway Clinical Research Center to enroll asthmatic and healthy volunteers for a prospective pilot study of differences in the airway microbiome between asthmatic and healthy individuals, and the impact of commonly prescribed therapies on the microbiome. She also will apply innovative, high-throughput approaches to perform phylogenetic and functional profiling of the airway microbiome in asthmatic patients. This research will lay important groundwork for future studies of the airway microbiome in larger populations of asthma patients or of specific asthma phenotypes.